Diagnostic criteria for tuberous sclerosis complex (TSC)

Genetic diagnostic criteriaEither TSC1 or TSC2 pathogenic# mutation in DNA from normal tissue
Clinical diagnostic criteria
 Major featuresHypomelanotic macules (≥3, ≥5 mm diameter)
Angiofibromas (≥3) or fibrous cephalic plaque
Ungual fibromas (≥2)
Shagreen patch
Multiple retinal hamartomas
Cortical dysplasias (includes tubers and cerebral white matter radial migration lines)
Subependymal nodules
Subependymal giant cell astrocytoma
Cardiac rhabdomyoma
Angiomyolipomas (≥2)+
 Minor features“Confetti” skin lesions
Dental enamel pits (>3)
Intraoral fibromas (≥2)
Retinal achromic patch
Multiple renal cysts
Nonrenal hamartomas
 DefiniteGenetic criteria
Two major features
One major feature with ≥2 minor features
 PossibleEither one major feature
≥2 minor features

LAM: lymphangioleiomyomatosis. #: defined as a mutation that clearly inactivates the function of the TSC1 or TSC2 proteins (e.g. out-of-frame insertion/deletion or nonsense mutation), prevents protein synthesis (e.g. large genomic deletion) or is a missense mutation whose effect on protein function has been established by functional assessment. Other TSC1 or TSC2 variants whose effect on function is less certain do not meet these criteria, and are not sufficient to make a definite diagnosis of TSC; : see table 3; +: a combination of LAM and angiomyolipomas without other features does not meet criteria for a definite diagnosis. Information from [1].